Uncontrolled Blood Pressure, Genetic Risk, and Alzheimer’s Disease

A new article published in JAMA: Neurology demonstrates a link between genetics, Alzheimer’s disease, and vascular problems.

There continues to be a large focus within dementia research to understand the link between heart health and brain health. This also is a growing area of research not only because most societies are aging (i.e., the average age of the population increases as people live longer and have fewer children) but also because many societies struggle with increasing obesity rates. Obesity and heart disease are strongly linked.

In addition, it has been well-established that people who have higher blood pressure are at greater risk of cognitive decline in old age and at greater risk for developing dementia. Such decline or dementia are believed to be caused, at least in part by, acute or chronic changes to the white matter of the brain. These changes are typically called small or silent strokes by physicians and are visible on magnetic resonance images (MRI) or CT scans. Due to the prevalence of white matter disease in dementia, diagnostic criteria for Alzheimer’s disease have been updated within the past few years to focus more on the role that cerebrovascular disease plays in the Alzheimer’s disease process.

In terms of genetics, the best-verified risk factor for Alzheimer’s disease relates to the apolipoprotein E4 (ApoE) genotype. Individuals who have two copies of the ApoE4 allele have up to a 12-fold increase risk for developing Alzheimer’s disease.

In order to officially diagnose someone as having Alzheimer’s disease, a postmortem pathology examination must be performed on the brain with results demonstrating the presence of groups of proteins called beta-amyloid (plaques) and what are called tau-driven neurofibrillary tangles (basically a twisting and changing of part of the internal structure of neurons – brain cells). While confirming the presence of these plaques and tangles requires pathological dissection, a type of brain scan called positron emission tomography (PET) imaging can be used to look at amount of beta-amyloid plaque build-up in living people.

What the researchers wanted to investigate is whether there is a link between having high blood pressure, the amount of beta-amyloid plaque people without Alzheimer’s disease have, and genetic risk (ApoE4). The researchers found weak and non-significant evidence that people with at least one ApoE4 allele had more plaque build-up in their brains as did people with hypertension. More importantly and significantly, those who had both genetic (ApoE4) and vascular (hypertension) risk had significantly more plaque in their brains. Further analyses showed that people without controlled high blood pressure were the ones who had the most plaque in their brains, on average. Again, the study population included middle-age and older adults without dementia at time of study participation.

What this study demonstrates is that middle- and old-aged people without cognitive difficulties who have genetic risk of developing Alzheimer’s disease (ApoE4 alleles) and who have high blood pressure show much more Alzheimer’s pathology in their brains. Much of this difference is driven by people who do not have well-controlled high blood pressure, meaning that if people have genetic risk of Alzheimer’s disease but do a good job of controlling blood pressure (keeping it under 140/90) do not have much more Alzheimer’s pathology than those without genetic risk and without (or with controlled) high blood pressure.

In summary, middle-age adults who have genetic risk factor for Alzheimer’s disease and who do not control high blood pressure are likely at much higher risk for developing Alzheimer’s disease later in life than those who keep blood pressure under control.


Rodrigue KM, Rieck JR, Kennedy KM, Devous MD, Diaz-Arrastia R, & Park DC (2013). Risk Factors for ?-Amyloid Deposition in Healthy Aging: Vascular and Genetic Effects. JAMA neurology, 70 (5), 600-6 PMID: 23553344

Image via Juan Gaertner / Shutterstock.

Jared Tanner, PhD

Jared Tanner has a Ph.D. in clinical psychology with an emphasis in neuropsychology. His interests are mainly neuroimaging and neuroanatomy. He spends his research time looking at the structure of gray and white matter in the brains of people with Alzheimer's disease and Parkinson's disease. With a focus on neuropsychology, he is also interested in how normal and abnormal brain structure relates to cognitive and behavioral functioning.
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